Table 2.

Compounds or drugs targeting mitochondrial pathways to restore apoptosis.

Compound or Drug	Mechanism	Target	Specific Cancer	Findings	Clinical Pipeline	Reference
Entinostat	Inhibits the function of histone deacetylases leading to more relaxed chromatin and gene expression	HDAC1/3	Osteosarcoma	Shown to upregulate the expression of Fas, leading to decreased pulmonary metastasis and improved outcomes	Preclinical	[93]
Venetoclax	Selective BCL-2 inhibitor that releases pro-apoptotic proteins	BCL-2	Acute myeloid leukemia	Overall response rate of 67% when combined with hypomethylating agents in elderly AML patients	FDA-approved, Phase III	[94]
MCL-1- specific inhibitor AZD5991	Binds directly to Mcl-1 and induces rapid apoptosis in cancer cells by activating the Bak-dependent mitochondrial apoptotic pathway	MCL-1	Myeloma and acute myeloid leukemia	Induces apoptosis in >80% of multiple MCL-1-dependent myeloma cell lines in vitro	Preclinical	[95]
Lenvatinib	Induces immunogenic cell death and activates TLR 3/4 ligands, enhancing immune response	TLR 3/4	Hepatocellular carcinoma	Triggers immunogenic cell death, enhancing anti-tumor immunity; increases T-cell activation and infiltration by 40% in HCC models	Preclinical	[96]
Obatoclax	Directly induces apoptosis through the activation of BAX/BAK following their release from the pro-survival BCL-2 members	Pan-BCL -2 family	Hematologic malignancies	Demonstrates tolerability and partial responses in patients with chronic lymphocytic leukemia and Hodkins lymphoma	Phase I clinical trial	[97]

Abbreviations: histone deacetylase 1/3 (HDAK1/3); B-cell lymphoma 2 (BCL-2); Myeloid Cell Leukemia 1 (MCL-1); acute myeloid leukemia (AML); Toll-like Receptors 3/4 (TLR3/4); hepatocellular carcinoma (HCC); Bcl-2-associated X protein/Bcl-2 antagonist/killer (BAX/BAK).